Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004024535 | SCV000673542 | uncertain significance | not specified | 2023-04-07 | criteria provided, single submitter | clinical testing | The p.E239Q variant (also known as c.715G>C), located in coding exon 3 of the GALNT12 gene, results from a G to C substitution at nucleotide position 715. The glutamic acid at codon 239 is replaced by glutamine, an amino acid with highly similar properties. This alteration was identified in a population-based colorectal cancer cohort. Authors performed a functional study assessing enzyme activity and determined that p.E239Q resulted in an approximate 2-fold decrease in enzyme activity; however, this was below the threshold for significance and not considered deleterious (Evans DR et al. Hum. Mutat. 2018 Aug;39(8):1092-1101). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV000764797 | SCV000895942 | uncertain significance | Colorectal cancer, susceptibility to, 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001230919 | SCV001403419 | uncertain significance | not provided | 2024-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 239 of the GALNT12 protein (p.Glu239Gln). This variant is present in population databases (rs777144221, gnomAD 0.02%). This missense change has been observed in individual(s) with rectal cancer (PMID: 29749045). ClinVar contains an entry for this variant (Variation ID: 485652). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GALNT12 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects GALNT12 function (PMID: 29749045). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001230919 | SCV002774602 | uncertain significance | not provided | 2024-04-12 | criteria provided, single submitter | clinical testing | The GALNT12 c.715G>C (p.Glu239Gln) variant has been reported in the published literature in an individual with rectal cancer and found to cause an approximately 2-fold decrease in GALNT12 enzyme activity in vitro, however the data lacked statistical significance (PMID: 29749045 (2018)). The frequency of this variant in the general population, 0.00019 (16/84952 chromosomes in European (Non-Finnish) subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Baylor Genetics | RCV000764797 | SCV004196154 | uncertain significance | Colorectal cancer, susceptibility to, 1 | 2024-02-07 | criteria provided, single submitter | clinical testing |